tbuckley/cabot-search huggingface dataset:
P1404: IL-10 PLUS THE EASIX SCORE PREDICT BLEEDING EVENTS AFTER ANTI-CD19 CAR T-CELL THERAPY
Authors: Xindi Wang, Chenggong LI, Wenjing Luo, Yinqiang Zhang, Zhongpei Huang, Jia Xu, Heng Mei, Yu Hu
Journal: HemaSphere (2023)

Topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical Background: Treatment-related coagulopathy is a major and frequent adverse event during chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell-associated coagulopathy (CARAC) is a clinical syndrome characterized by bleeding and/or thrombosis accompanied by decreased platelets (PLTs) and coagulopathy, which occurs mainly within 28 days after CAR-T cell infusion. During CAR T-cell treatment, more than 50% of patients will experience thrombocytopenia or have at least one coagulation abnormality. CARAC can cause bleeding events. Notably, the endothelium is important for maintaining homeostasis in the coagulation system. Endothelial activation triggers fluctuations in coagulation and participate in bleeding events. Aims: To explore risk factors for hemorrhage after CAR T-cell therapy. Methods: We retrospectively analyzed routine indicators in 56 patients with non-Hodgkin lymphoma and B-cell acute lymphoblastic leukemia who received anti-CD19 CAR T-cell therapy (NCT04008251). The grading of thrombocytopenia, hypofibrinogenemia, increased international normalized ratio, and prolonged activated partial thromboplastin time was according to Common Terminology Criteria for Adverse Events, version 5.0. The rating assessment of D-dimer, thrombin time, prothrombin time (PT), antithrombin III, and fibrinogen degradation products referred to the classification as previously used. The grading of bleeding events was according to the World Health Organization bleeding criteria. In addition, we employed logistic regression to screened risk variables. Results: Disturbance of coagulation occurred mainly within one month post infusion, especially on day 7 and 14. The cumulative incidence of bleeding events within one month was 32.8% (Figure 1A), with the median onset of 7 (range, 0–28) days. Patients experienced bleeding events within one month had longer PT, higher interleukin (IL) -6, higher IL-10, and lower PLTs before lymphodepletion. There were also correlations among coagulation-, inflammatory-, and tumor burden-related markers (Figure 1B). Multivariate analysis showed IL-10 (> 7.98 pg/mL; adjusted odds ratio [OR], 10.61; 95% confidence interval [CI], 1.49–75.40; P = 0.018) and the endothelial activation and stress index (EASIX, defined as dehydrogenase [U/L] × creatinine [mg/dL]/ platelets [×109 cells/L]; >7.65; adjusted OR, 7.47; 95% CI, 1.00–55.95; P = 0.050) were significant risk factors for bleeding events. IL-10 plus the EASIX defined three risk groups for bleeding events with cumulative incidence of 100% (hazard ratio [HR], 14.47; 95% CI, 2.78–75.29; P < 0.0001), 38.5% (HR, 3.68; 95% CI, 0.82–16.67; P = 0.089), and 11.8% (reference), respectively (Figure 1C). Summary/Conclusion: IL-10 plus the EASIX score could predict bleeding events after anti-CD19 CAR T-cell therapy.Keywords: Cellular therapy
P1541: CONVALESCENCE NEW LIQUID COOLING THERAPY ON PREVENTION AND TREATMENT OF CHEMOTHERAPEUTIC ORAL MUCOSITIS
Authors: Yang He, Fangfang Wu, Aihua Sun
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: With the in-depth research on the basic and clinical aspects of hematopoietic stem cell transplantation, the technology of stem cell transplantation has been vigorously developed, and more and more colleagues have paid attention to chemotherapy-related oral mucositis. How to prevent and reduce chemotherapy-related oral mucositis has become one of the urgent problems to be solved in the medical care of hematopoietic stem cell transplantation. Aims: To investigate the clinical effect of granulocyte colony stimulating factor combined with Kangfuxin liquid cooling therapy on the prevention and treatment of chemotherapy-associated oral mucositis, and to summarize the experience. Methods: 162 patients who underwent hematopoietic stem cell transplantation in our department from 2022.1.1 to 2022.12.31 were selected and divided into control group and experimental group according to the order of admission. The control group consisted of 91 patients who checked in from 2022.1.1 to 2021.06.31. Routine nursing measures for prevention and treatment of chemotherapy-related oral mucositis were adopted. The experimental group included 71 patients who checked in from 2022.7.1 to 2022.12.31. On the basis of routine nursing measures, granulocyte colony stimulating factor was added in combination with rehabilitation new liquid cooling therapy. There was no difference in gargle frequency, gargle timing and gargle duration between the two groups. The incidence, grade, healing time, pain degree and duration of chemotherapy - related oral mucositis were compared between the two groups. Results: In the control group, 59 patients with chemotherapy-related oral mucicitis occurred, the incidence rate was 64.83%, including 12 patients with grade 1 (13.18%), 36 patients with grade 2 (39.56%), 8 patients with grade 3 (8.79%), and 3 patients with grade 4 (3.29%). In the experimental group, 39 patients with chemotherapy-related oral mucitis occurred, with an incidence of 54.92%, including 11 patients with grade 1 (15.49%), 20 patients with grade 2 (28.16%), 7 patients with grade 3 (9.85%), and 1 patient with grade 4 (1.41%). The ulcer healing time of the control group was 7.28 + 1.57 days, and that of the experimental group was 4.63 + 1.13 days, the difference was statistically significant (P<0.05). Summary/Conclusion: Granulocyte colony stimulating factor combined with convalescing new liquid cooling therapy can effectively prevent and treat oral mucositis associated with chemotherapy, reduce the occurrence and severity of oral mucositis, accelerate the healing time of ulcers, and alleviate patients’ pain, and is worthy of clinical application. Keywords: Granulocyte colony-stimulating factor (G-CSF)
Research on ferroptosis as a therapeutic target for the treatment of neurodegenerative diseases
Authors: Yi Wang, Meng-nan Lv, Wei-jiang Zhao
Journal: Ageing Research Reviews (2023)

Ferroptosis is an iron- and lipid peroxidation (LPO)-mediated programmed cell death type. Recently, mounting evidence has indicated the involvement of ferroptosis in neurodegenerative diseases, especially in Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and so on. Treating ferroptosis presents opportunities as well as challenges for neurodegenerative diseases. This review provides a comprehensive overview of the underlying mechanisms that contribute to the occurrence of ferroptosis, as well as their implications in the pathogenesis and advancement of major neurodegenerative disorders. Meanwhile, we summarize the interaction between ferroptosis and other types of cell death in the advancement of neurodegenerative diseases and their contribution to corresponding drug development. In addition, we specifically summarize recent advances in developing therapeutic means targeting ferroptosis in these diseases, which may guide future approaches for the effective management of these devastating medical conditions.
Colorectal Cancer Stage Distribution at First and Repeat Fecal Immunochemical Test Screening
Authors: Arthur Kooyker, Lucie de Jonge, Esther Toes-Zoutendijk, Manon Spaander, Hanneke van Vuuren, Ernst Kuipers, Folkert van Kemenade, Chris Ramakers, Evelien Dekker, Iris Nagtegaal, Monique van Leerdam, Iris Lansdorp-Vogelaar
Journal: Clinical Gastroenterology and Hepatology (2023)

Background & AimsFor colorectal cancer (CRC) screening to be effective, it is important that screen-detected cancers are found at an early stage. Studies on stage distribution of screen-detected CRC at repeat screening of large population-based fecal immunochemical test (FIT)-based screening programs and the impact of FIT cut-off values on staging currently are lacking.MethodsWe obtained data for FIT-positive participants (FIT cut-off, 47 μg hemoglobin/g feces) at their first or second (ie, repeat) screening from the Dutch National Screening Database from 2014 to 2018. Tumor characteristics were acquired through linkage with The Netherlands Cancer Registry. We compared stage at diagnosis (I–II vs III–IV) of CRCs detected at a first or second screening. In addition, we analyzed the hypothetical yield and stage distribution of CRC for different FIT cut-off values up to 250 μg hemoglobin/g feces.ResultsAt the first and second screenings, respectively, 15,755 and 3304 CRCs were detected. CRCs detected at the first or second screening were equally likely to be stages I to II (66.5% vs 67.7%; relative risk, 1.02; 95% CI, 1.00–1.05). A hypothetical increase of the FIT cut-off value from 47 μg to 250 μg resulted in a reduction of detected CRCs by 88.3% and 79.0% at the first or second screening, respectively. Even then, the majority of detected CRCs (63%–64%) still would be diagnosed at stages I to II.ConclusionsFIT-based screening is effective in downstaging CRC, and also at repeat screening. Increasingly, the FIT cut-off level has a limited impact on the stage distribution of detected CRCs, although it greatly affects CRC detection and thus is important to keep low.Graphical abstract
Different prognostic values of KRAS exon 2 submutations and BRAF V600E mutation in microsatellite stable (MSS) and unstable (MSI) stage III colon cancer: an ACCENT/IDEA pooled analysis of seven trials
Authors: J. Taieb, F.A. Sinicrope, L. Pederson, S. Lonardi, S.R. Alberts, T.J. George, G. Yothers, E. Van Cutsem, L. Saltz, S. Ogino, R. Kerr, T. Yoshino, R.M. Goldberg, T. André, P. Laurent-Puig, Q. Shi
Journal: Annals of Oncology (2023)

The prognostic value of KRAS and BRAF
HER2-low expression in patients with advanced or metastatic solid tumors
Authors: B. Uzunparmak, C. Haymaker, G. Raso, S. Masciari, L. Wang, H. Lin, A. Gorur, B. Kirby, A.-M. Cimo, A. Kennon, Q. Ding, G. Urschel, Y. Yuan, G. Feng, Y. Rizvi, A. Hussain, C. Zhu, P. Kim, G. Abbadessa, V. Subbiah, T.A. Yap, J. Rodon, S.A. Piha-Paul, F. Meric-Bernstam, E.E. Dumbrava
Journal: Annals of Oncology (2023)
Combination of bacterial-targeted delivery of gold-based AIEgen radiosensitizer for fluorescence-image-guided enhanced radio-immunotherapy against advanced cancer
Authors: Yanhong Duo, Zide Chen, Zihuang Li, Xing Li, Yaoqiang Yao, Tianzhao Xu, Ge Gao, Guanghong Luo
Journal: Bioactive Materials (2023)

Aggregation-Induced Emission luminogen (AIEgen) possess great potential in enhancing bioimaging-guided radiotherapeutic effects and radioimmunotherapy to improve the therapeutic effects of the tumor with good biosafety. Bacteria as a natural carrier have demonstrated great advantages in tumor targeted delivery and penetration to tumor. Herein, we construct a delivery platform that Salmonella VNP20009 act as an activated bacteria vector loaded the as-prepared novel AIEgen (TBTP-Au, VNP@TBTP-Au), which showed excellent radio-immunotherapy. VNP@TBTP-Au could target and retain AIEgen at the tumor site and deliver it into tumor cells specially, upon X-ray irradiation, much ROS was generated to induce immunogenic cell death via cGAS-STING signaling pathway to evoke immune response, thus achieving efficient radioimmunotherapy of the primary tumor with good biosafety. More importantly, the radioimmunotherapy with VNP@TBTP-Au formatted good abscopal effect that was able to suppress the growth of distant tumor. Our strategy pioneer a novel and simple strategy for the organic combination of bacteria and imaging-guided radiotherapy, and also pave the foundation for the combination with immunotherapy for better therapeutic effects.
Intravesical chemotherapy synergize with an immune adjuvant by a thermo-sensitive hydrogel system for bladder cancer
Authors: J. Liu, T.Y. Yang, L.Q. Dai, K. Shi, Y. Hao, B.Y. Chu, D.R. Hu, Z.W. Bei, L.P. Yuan, M. Pan, Z.Y. Qian
Journal: Bioactive Materials (2023)

Surgical resection remains the prefer option for bladder cancer treatment. However, the effectiveness of surgery is usually limited for the high recurrence rate and poor prognosis. Consequently, intravesical chemotherapy synergize with immunotherapy in situ is an attractive way to improve therapeutic effect. Herein, a combined strategy based on thermo-sensitive PLEL hydrogel drug delivery system was developed. GEM loaded PLEL hydrogel was intravesical instilled to kill tumor cells directly, then PLEL hydrogel incorporated with CpG was injected into both groins subcutaneously to promote immune responses synergize with GEM. The results demonstrated that drug loaded PLEL hydrogel had a sol-gel phase transition behavior in response to physiological temperature and presented sustained drug release, and the PLEL-assisted combination therapy could have better tumor suppression effect and stronger immunostimulating effect in vivo. Hence, this combined treatment with PLEL hydrogel system has great potential and suggests a clinically-relevant and valuable option for bladder cancer.
P1188: DYNAMIC CHANGES IN CIRCULATING EBV-DNA LOAD DURING TREATMENT HAVE PROGNOSTIC VALUES IN EBV+ DLBCL-NOS: A CHINESE COHORT STUDY
Authors: Tong-Yao Xing, Zi-Wen Duan, Jia-Zhu Wu, Haorui Shen, Hua Yin, Yue LI, LI Wang, Jianyong LI, Jinhua Liang, Wei Xu
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: EBV-positive diffuse large B-cell lymphoma, not otherwise specified (EBV+ DLBCL-NOS), is an EBV-positive clonal B-cell lymphoid proliferation and circulating EBV-DNA is a great indicator for prognosis among EBV associated disease. However, the prognostic role of EBV DNA for EBV+ DLBCL-NOS was not identified, especially the dynamic change of EBV-DNA. Aims: Therefore, we conducted this retrospective study to explore the prognostic role of circulating EBV-DNA in EBV+ DLBCL-NOS patients and we specially focused on the potential capacity of the dynamic changes in circulating EBV DNA as a biomarker for therapeutic response and prognostication. Methods: In this retrospective study, we report 66 EBV+ DLBCL cases among 2137 DLBCL-NOS cases diagnosed from 2013 to 2021 (prevalence of 6.0%). The peripheral whole blood sample was collected for each patient at these time points: at initial diagnosis before treatment, after 3 cycles of treatment, at the end of treatment, and during the follow-up. EBV-DNA copy number in whole blood was quantified by a real-time quantitative PCR. The detection sensitivity was 500 copies per ml and EBV-DNA copy number less than 500 copies/ml was defined as negative. Results: After a median follow-up of 27 months, progression-free survival (PFS) and overall survival (OS) at 2 years were 39.5% ± 6.2% and 53.6% ± 6.4%, respectively (Figure 1A, 1B). According to the pretreatment EBV-DNA status, the pretreatment EBV-DNA positive group and pretreatment EBV-DNA negative group had comparable PFS and OS (P=0.7726 and P=0.9040, respectively) (Figure 1C, 1D). Dynamic changes in circulating EBV-DNA copy number were available for 58 out of 66 patients. Patients were divided into three subgroups according to dynamic changes of EBV-DNA status: EBV-DNA persistently negative group (PNG, 24/58), EBV-DNA persistently positive group (PPG, 16/58), and EBV-DNA transformed from positive to negative group (TNG, 18/58); among the three groups, PPG had a clear trend toward worse PFS and OS (P=0.0527 and P=0.0139, respectively) (Figure 1E, 1F). Decline in EBV copies correlated significantly with treatment response as well; it is noteworthy that dynamic changes of pretreatment EBV-DNA positivity cases rather than post treatment EBV-DNA status were strongly associated with therapy response of CR (P=0.034 and P=0.086, respectively) (Figure 2G).Summary/Conclusion: In conclusion, circulating EBV-DNA level played a vital role in prognostic and monitoring marker for EBV+ DLBCL-NOS. Keywords: DLBCL, EBV
Treatment strategies and drug resistance mechanisms in adenocarcinoma of different organs
Authors: Peng Xing, Shuo Wang, Yu Cao, Bo Liu, Feifei Zheng, Wei Guo, Junhao Huang, Zimo Zhao, Ziyi Yang, Xingda Lin, Liang Sang, Zhe Liu
Journal: Drug Resistance Updates (2023)

Adenocarcinoma is a common type of malignant tumor, originating from glandular epithelial cells in various organs, such as pancreas, breast, lung, stomach, colon, rectus, and prostate. For patients who lose the opportunity for radical surgery, medication is available to provide potential clinical benefits. However, drug resistance is a big obstacle to obtain desired clinical prognosis. In this review, we provide a summary of treatment strategies and drug resistance mechanisms in adenocarcinoma of different organs, including pancreatic cancer, gastric adenocarcinoma, colorectal adenocarcinoma, lung adenocarcinoma, and prostate cancer. Although the underlying molecular mechanisms involved in drug resistance of adenocarcinoma vary from one organ to the other, there are several targets that are universal for drug resistance in adenocarcinoma, and targeting these molecules could potentially reverse drug resistance in the treatment of adenocarcinomas.
P1165: PRELIMINARY FINDINGS OF A PHASE Ⅱ STUDY OF CHEMO-FREE COMBINATION OF POMALIDOMIDE, ORELABRUTINIB, RITUXIMAB WITH SEQUENTIAL HIGH-DOSE METHOREXATE IN NEWLY DIAGNOSED PRIMARY CNS LYMPHOMA
Authors: Yan Zhang, Chao Chen, Danqing Zhao, Zhe Zhuang, Chong Wei, Wei Wang, Wei Zhang, Dao-Bin Zhou
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: High-dose methotrexate (HD-MTX) is widely used as front-line treatment in patients with primary central nervous system lymphoma (PCNSL). Both preclinical models and clinical data suggested pomalidmide and orelabrutinib were effective in PCNSL and the combination of them may have synergy in DLBCL. Aims: We aimed to evaluate the tolerability and efficacy of pomalidomide, orelabrutinib and rituximab (POR) with the sequential addition of HD-MTX chemotherapy in newly diagnosed PCNSL. Methods: This is an investigator-initiated, single-arm phase II study, and immunocompetent patients with untreated PCNSL were enrolled. Patients were treated with pomalidomide 4mg once per day on days 1-14, orelabrutinib 150 mg once daily continuously, and rituximab 375 mg/m2 intravenous once on day 1 of each 21-day cycle. After four cycles, HD-MTX chemotherapy was sequentially added for two additional cycles. The primary endpoint was overall response rate (ORR) at the end of four cycles of POR. Circulating tumor DNA detection of cerebrospinal fluid was performed. This trial was registered at www.clinicaltrials.gov (#NCT 05390749). Results: The data cut-off date was 15th Feb 2023, and thirteen patients were enrolled in this study. The median age was 58 years (range, 34-79 years). Four patients had eye involvement and one patient had leptomeninges involvement. Eight patients performed ctDNA analysis and all had MYD88 l265p mutation. One patient discontinued the experimental treatment due to treatment-related adverse events (TRAE) and eleven patients finished four cycles of POR and were evaluable. The ORR after four cycles of POR was 90.1% and the complete response rate was 36.4%. Twelve patients who finished at least 1 cycle were evaluated for safety analysis. The most common grade 3 or 4 AEs were neutropenia (G3,n=1; G4, n=2), thrombocytopenia (G3, n=2), rash(G3 n=1, G4 n=1), ALT increased (G3, n=1) and anemia(G3,n=1). With a median follow-up of 4 months, one patient relapsed and died of PCNSL. Summary/Conclusion: This is the first study to treat newly diagnosed PCNSL with a targeted therapy combination before chemotherapy. POR produced a high ORR with good tolerance. This suggested the potential of noncytotoxic first-line therapies for PCNSL. Funding: CAMS Innovation Fund for Medical Sciences（CIFMS）2021-I2M-C&T-B-005. *Corresponding author Dao-bin Zhou Address: Shuaifuyuan No. 1, Dongcheng District, Beijing, China. Tel: +86 13901113623 Keywords: Lymphoma therapy, Non-Hodgkin’s lymphoma, CNS lymphoma
P1114: HIGHLY SELECTIVE ALLOSTERIC MODULATOR OF THE PHOSPHOINOSITIDE 3-KINASE DELTA (PI3KΔ) ROGINOLISIB (IOA-244) IN A DOSE ESCALATION STUDY OF PATIENTS WITH REFRACTORY/RELAPSED FOLLICULAR LYMPHOMA (FL)
Authors: Carmelo Carlo-Stella, Michael Lahn, Tracey Hammett, Lars van der Veen, Rebeca Zorrilla, Catherine Pickering, Armando Santoro
Journal: HemaSphere (2023)

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Roginolisib has shown a favourable toxicity and ADME profile in over 30 patients (pts) with solid tumours. Using the recommended phase 2 dose (RP2D) established in pts with solid tumours, the 80 mg QD dose was given to patients with FL. Aims: As part of the First-in-human (FiH) dose escalation study, pts with FL were treated with the RP2D to determine whether same treatment regimen can be used in either solid or FL pts (Di Giacomo et al 2021). Methods: In Part A of the FiH dose escalation study, roginolisib was investigated at 20 and 80 mg QD in pts with FL. Part B consists of expansion cohorts of specific tumour indications, including pts with lymphoma, and is not reported here. Primary objective: safety of the RP2D established in solid tumour pts. Secondary objectives: PK; PD (e.g., changes in immune cell subsets in peripheral blood); Lugano-based responses; PFS and OS. Results: In Part A for pts with FL, there were two cohorts: (a) Cohort 1: 20 mg QD daily (4/4; 2 female, 2 male); (b) Cohort 2: 80 mg QD (4/4; 3 female, 1 male). There were no DLT and no dose modifications. The mean time on treatment was 1.9 mo (20 mg QD) and 3.4 mo (80 mg QD), with one patient at the 80 mg still on treatment after 5 mo). More than 4 prior lines of treatment were in 3/8 pts. Transient (lasting less than 48 hrs) platelet reduction (G3) and AST/ALT elevation (G3) were observed in 2/8 pts, which improved while pts were on therapy and no treatment intervention was needed. PRs were observed in 2/4 pts at the 80 mg QD dose and none at the 20 mg QD. Summary/Conclusion The safety profile of roginolisib in pts with FL appears to match that in pts with solid malignancies. In contrast to other PI3Kd inhibitors, IOA-244 is highly selective and uniquely functions as a allosteric modulator. Hence, roginolisib delivers a selective inhibition of its target without off-target effects induced by inhibition of other PI3K isoenzymes Keywords: Follicular lymphoma